Insights into the mechanism and regulation of EgtD, a novel histidine methyltransferase from ergothioneine biosynthesis

My PhD thesis was centered around the biosynthetic origin of amino acid betaines. This ubiquitous and divers class of simple natural products plays key roles in many aspects of cellular life. These compounds are also increasingly recognized as green and sustainable additives in foods, cosmetics, detergents or ionic liquids. We discovered and characterized a class of N-methyl transferases that allow a select group of microorganisms to produce a variety of trimethylated amino acids. Through structural, kinetic and bioinformatics analysis we were able to delineate the catalytic mechanism and functional diversity of this novel enzyme family of betaine synthases. The results and insights of my thesis pave the way to explore the biological function of amino acid betaines, and also describe the first biotechnological approach for bulk production of these natural products

Anaerobic Origin of Ergothioneine

Ergothioneine is a sulfur metabolite that occurs in microorganisms, fungi, plants, and animals. The physiological function of ergothioneine is not clear. In recent years broad scientific consensus has formed around the idea that cellular ergothioneine primarily protects against reactive oxygen species. Herein we provide evidence that this focus on oxygen chemistry may be too narrow. We describe two enzymes from the strictly anaerobic green sulfur bacterium Chlorobium limicola that mediate oxygen-independent biosynthesis of ergothioneine. This anoxic origin suggests that ergothioneine is also important for oxygen-independent life. Furthermore, one of the discovered ergothioneine biosynthetic enzymes provides the first example of a rhodanese-like enzyme that transfers sulfur to non-activated carbon